Treatment of erythrodermic psoriasis with etanercept

BACKGROUND: Severe variants of psoriasis, such as erythrodermic psoriasis, may be associated with serious morbidity and mortality. Current treatment options for erythrodermic psoriasis are limited, unsatisfactory and potentially associated with organ-specific toxicity. Recently, a new class of agents, targeted biological therapies, has emerged. Etanercept is a recombinant human fusion protein acting as a competitive inhibitor of tumour necrosis factor-alpha. The safety and efficacy of etanercept have been widely demonstrated in psoriatic arthritis and moderate to severe plaque-type psoriasis. OBJECTIVES: To assess the efficacy and tolerability of etanercept in the treatment of erythrodermic psoriasis over a period of 24 weeks. METHODS: Ten patients, eight men and two women, were selected to receive etanercept 25 mg subcutaneously twice weekly. The Psoriasis Area and Severity Index (PASI) score, ranging from 0 to 72, was used to assess the severity of disease. RESULTS: Etanercept was well tolerated and led to a significant reduction in the severity of disease over the period of treatment. After 24 weeks, the mean PASI score decreased from 39.1 (baseline) to 5.1. At week 12, five of 10 (50%) patients achieved an improvement of PASI score from baseline exceeding 75%. At week 24, six of 10 patients (60%) achieved or maintained an improvement of PASI score from baseline exceeding 75% while two patients (20%) maintained an improvement of between 50% and 75%. CONCLUSIONS: In this study, etanercept has been demonstrated to be an effective treatment for erythrodermic psoriasis, providing a safe and convenient alternative to current therapies.     

Comparative Efficacy of Biologics in Psoriasis

Background: Psoriasis is a chronic, immune-mediated skin disease that also has systemic manifestations. Safe and effective long-term treatments are needed. Biologic treatments that inhibit the immunopatho-genesis of psoriasis have helped meet this need. Purpose: The purpose of this study was to compare the efficacy of biologic therapies used for psoriasis. Methods: A literature search was performed using PubMed and the keywords ‘(PASI-75 OR efficacy) AND psoriasis AND (adalimumab OR alefacept OR etanercept OR infliximab OR ustekinumab).’ Randomized, double-blind, and placebo-controlled studies on US FDA-approved biologics were selected. Studies assessing the proportion of subjects achieving 75% improvement in Psoriasis Area and Severity Index (PASI-75) within a 12-week period were included. Studies on pediatric populations and psoriatic arthritis were excluded. The weighted average of PASI-75 for each reported regimen was calculated to determine the efficacy of biologic agents used for moderate-to-severe psoriasis. Tolerance and secondary efficacy measures were also examined for the selected studies. Results: FDA-approved regimens of adalimumab, infliximab, ustekinumab, and alefacept were effective in treating moderate-to-severe psoriasis. Weighted average PASI-75 scores for infliximab, ustekinumab, adalimumab, etanercept, and alefacept were 78.6%, 72.1%, 70.5%, 48.1%, and 21%, respectively. Limitations: The comparative efficacy of biologic agents data was limited to 12 weeks, thus generalizing the results to longer treatment periods may not be accurate. Conclusions: Various biologic agents for psoriasis were effective at 12 weeks in placebo-controlled trials. Available data cannot fully account for situations in clinical practice, in which combination and longer duration of therapy may be required. When choosing the most effective or best agent, multiple factors should be considered including patient preference, cost, tolerance, adverse effects, dosing schedule, and mode of administration.     

Adalimumab for psoriasis patients who are non-responders to etanercept: open-label prospective evaluation

Background  Targeted biologic therapies have made a significant impact on the treatment for moderate to severe psoriasis. In the United Kingdom, the National Institute for Health and Clinical Excellence recommends etanercept, a human recombinant tumour necrosis factor (TNF) receptor fusion protein, for moderate to severe psoriasis patients who have failed conventional therapies. There is, however, no data available on the role of other TNF antagonists for patients who have failed etanercept. Adalimumab, a fully human, anti-TNF monoclonal antibody, is approved for treatment of moderate to severe psoriasis.
Objectives  To assess the efficacy and safety of adalimumab (40 mg weekly) in psoriasis patients who were non-responders to high-dosage etanercept (50 mg twice weekly).
Methods  All patients attending a tertiary referral service for severe psoriasis who were non-responders to high-dosage etanercept [i.e. failed to achieve ≥ 50% improvement in Psoriasis Area and Severity Index (PASI 50) after 12 weeks of treatment] were considered for open-label adalimumab therapy for 12 weeks. Details on clinical course, PASI, Dermatology Life Quality Index (DLQI) and adverse events were recorded at baseline and weeks 2, 4, 8, and 12.
Results  Four of five patients in this study had reached at least PASI 50 by week 12. Of these, two patients achieved a 75% improvement in PASI (PASI 75). No serious adverse events were reported.
Conclusions  Initial data from this open-label prospective evaluation suggests that weekly adalimumab therapy is an effective treatment for patients with severe psoriasis who had failed to respond to at least 3 months of high-dosage etanercept.     

Our experience with etanercept in the treatment of psoriasis

Psoriasis is a chronic inflammatory disorder that usually requires long-term control. Etanercept has been shown to be effective in this disease. The efficacy and safety of etanercept were assessed in patients with psoriasis. In this 16-week open clinical trial, 29 patients with clinically stable psoriasis and psoriatic arthritis received etanercept (25 mg twice weekly) subcutaneously. All patients were evaluated for the psoriasis area, severity index (PASI) and Ritchie's articular index (RAI) which measures arthritis disease activity. Improvement by 75 percent in PASI, considered significant for psoriasis remission, was observed in nearly sixty percent of patients after 12-week etanercept therapy. The percentage of PASI improvement was nearly 25% at two weeks, 52.3% at four weeks and 78% at 12 weeks of etanercept treatment, and was maintained for the next four weeks. Comparable results were obtained in the improvement of psoriatic arthritis symptoms, as improvement of 75 percent in RAI was observed in 58.3 percent of patients after 12 weeks of etanercept therapy. The percentage of RAI improvement was nearly 26% at two weeks, 40.5% at four weeks and 73.6% at 12 weeks and 77.1% at 16 weeks of etanercept treatment. Etanercept was generally well tolerated, as most events were of mild severity. The treatment with etanercept led to significant improvement in patients with psoriasis over a period of 16 weeks.     

Etanercept

Etanercept (Enbrel), a tumor necrosis factor-alpha antagonist produced by recombinant technology, is approved for use in the US as subcutaneous monotherapy in adults with moderate-to-severe psoriasis who are candidates for systemic therapy or phototherapy. The drug is also indicated in patients with psoriatic arthritis, in whom it may be used in combination with methotrexate. In well designed trials in patients with moderate-to-severe psoriasis, short-term etanercept therapy (typically 25 or 50 mg twice weekly) significantly increased the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index score compared with placebo. Similarly, in well designed trials in patients with psoriatic arthritis, treatment with short-term etanercept 25 mg twice weekly, alone or in combination with methotrexate, improved clinical features of the disease, while radiographic progression of joint damage appeared to be significantly slowed in a nonblind 1-year extension. Short-term etanercept therapy was well tolerated in patients with psoriasis or psoriatic arthritis. Etanercept is thus a valuable new option for the treatment of patients with chronic moderate-to-severe plaque psoriasis (who are candidates for systemic therapy or phototherapy or have failed other systemic therapies) or with psoriatic arthritis.     

Treatment with 311-nm ultraviolet B accelerates and improves the clearance of psoriatic lesions in patients treated with etanercept

Background  Some patients with plaque-type psoriasis respond slowly to treatment with etanercept. In such cases combining etanercept with conventional treatments might be helpful.
Objectives  To investigate whether treatment with 311-nm ultraviolet (UV) B can improve the therapeutic response in patients treated with etanercept.
Methods  Four women and one man (mean age 57 years, range 48–66) with moderate to severe plaque-type psoriasis who had received standard treatment with etanercept 50 mg twice weekly for 6 weeks without Psoriasis Area and Severity Index (PASI) reduction of 75% or greater (of initial mean PASI of 16·0, range 15·4–20·4) were enrolled in the study. Starting at 6 weeks, 311-nm UVB treatment was given to a randomly selected body half (left or right, excluding the head) for another 6 weeks, while all patients continued receiving etanercept. The patients were monitored by half-body PASI at weekly intervals.
Results  During the 6-week irradiation regimen, 311-nm UVB significantly bolstered the therapeutic response in the patients on etanercept treatment. After 6 weeks of 311-nm UVB, the patients had a mean PASI on their UV-irradiated body halves of 1·6 (range 0·6–3·3) vs. 4·7 (range 1·4–8·6) on nonirradiated body halves ( P  =   0·0192, paired two-tailed t -test), compared with 10·7 (range 6–16·4) and 10·5 (range 5·2–16·4) at start of 311-nm UVB treatment. The overall mean PASI reduction from baseline (i.e. at etanercept start) was 89% vs. 68%, respectively ( P  =   0·0009 and P  =   0·0088).
Conclusions  Treatment with 311-nm UVB significantly accelerates and improves the clearance of psoriatic lesions in patients responding slowly to etanercept monotherapy.     

Efficacy and Tolerability of a Cosmetically Acceptable Coal Tar Solution in the Treatment of Moderate Plaque Psoriasis

Background: Topical coal tar is awell known and effective treatment for psoriasis, but the messiness, staining, odor, and inconvenience associated with its use make patient satisfaction and compliance a challenge. Objective: To determine the efficacy, patient tolerability, and cosmetic acceptability of a new topical liquor carbonis distillate (LCD) 15% solution compared with calcipotriene (calcipotriol) cream in patients with moderate, chronic plaque psoriasis. Study Design: A randomized, single-blind, active-controlled, parallel-group, clinical trial consisting of a 12-week treatment phase and a 6-week post-treatment follow-up phase. Setting: Outpatient dermatology research unit in an academic hospital. Patients: Sixty adults with moderate, chronic plaque psoriasis (3–15% body surface area affected) not receiving other psoriasis therapies. Intervention: Patients were randomized to apply either an LCD 15% solution (Psorent®) or a commercially available calcipotriene 0.005% cream (Dovonex®) to their psoriasis areas (excluding the head) twice daily at home for 12 weeks. Assessments: A blinded investigator evaluated the patients’ psoriasis using a modified Psoriasis Area and Severity Index (PASI) that excluded the head, and a Physician’s Global Assessment (PGA) scale at weeks 0 (baseline), 2, 4, 8, and 12 (end of treatment), and 18 (6 weeks after treatment was withdrawn). Patients assessed their psoriasis symptoms and quality of life and completed a cosmetic acceptability survey about their medication. Outcome Measures: The changes in the baseline PASI scores after 12 weeks of treatment were compared between LCD and calcipotriene groups. Additional comparisons were performed for success rates during treatment (PASI 75 and PASI 50), changes in PGA scores, patient-reported psoriasis symptom scores, patients’ quality-of-life scores, and recurrence rates during post-treatment follow-up. Results: Both treatment groups showed improvement in psoriasis severity and quality of life. However, the LCD group had greater mean reductions in PASI scores: 58% vs 37% in the calcipotriene group (p < 0.05) at week 12. Additionally, the LCD group had more patients (14/27) with absent or minimal psoriasis on the PGA scale than the calcipotriene group (6/28) by the end of treatment (p < 0.05). LCD-treated patients also maintained their improvement better than calcipotriene-treated patients through week 18 after treatment was withdrawn for 6 weeks. Both treatments were well tolerated and cosmetically acceptable to patients. Conclusion: The newly formulated LCD solution, applied twice daily at home for 12 weeks, was more effective and as well tolerated and cosmetically acceptable as the calcipotriene cream over 12 weeks of treatment and 6 weeks of follow-up. The LCD solution is a patient-accepted and effective corticosteroid-sparing treatment alternative for psoriasis patients. Clinical Trial Registration Identifier: NCT00705900     

Clinical experience with etanercept in the treatment of psoriasis

BackgroundEtanercept is one of the new biologic agents available for treating psoriasis. It has proved an effective option in a high percentage of patients, leading to sustained improvements in the psoriasis area severity index (PASI). Likewise, it is effective at controlling psoriatic arthritis, and its safety profile is excellent, with a much lower specific organ toxicity than traditional drugs and few side effects. Many of the data published to date are derived from clinical trials with this medication, but further studies are needed on the use of this therapy to manage patients in daily clinical practice.MethodsThis was a retrospective observational study of 36 patients with psoriasis who received etanercept between March 2004 and March 2006. We describe the experience of using this agent at our hospital, with the clinical outcomes and the problems we have faced.ResultsThe PASI score was assessed before treatment and at 3 and 6 months of patient follow-up. After 3 months of treatment, 13 patients (36.11 %) had achieved a 50 % improvement in PASI score (PASI₅₀), and 16 patients (44 %) had achieved a 75 % improvement (PASI₇₅). Two of the patients (5.56 %) experienced an improvement in their disease without reaching PASI₅₀ and only 4 patients (11.11 %) did not show clinical improvement or deteriorated. After 6 months, efficacy improved, with 27 patients (75 %) achieving PASI₇₅, 6 patients (16.67 %) achieving PASI₅₀, and 2 patients (5.56 %) showing no benefit from treatment. After 6 months, 13 of the patients (36.1 %) had achieved a 90 % improvement in PASI score. No adverse events of sufficient significance to warrant discontinuation of treatment were reported. At present, 11 of the patients remain on etanercept treatment as efficacy has been sustained and they have not experienced any adverse events of note.ConclusionsOur clinical experience with the use of etanercept for treating plaque psoriasis shows a favorable efficacy and safety profile. We propose a standardized procedure for consultations with psoriasis patients involving extensive data collection on each visit and the creation of a national surveillance system for patients under treatment with biologic agents.     

A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction

BACKGROUND: In previous studies, etanercept significantly improved plaque psoriasis and was well tolerated. OBJECTIVES: To examine further the efficacy and safety of etanercept and to assess maintenance of treatment effect after dose reduction of etanercept. METHODS: In this multicentre 24-week study in the U.S.A., Canada and Western Europe, patients were at least 18 years old; had active, clinically stable plaque psoriasis involving at least 10% of body surface area; had a minimum Psoriasis Area and Severity Index (PASI) of 10 at screening; and had received or were a candidate to receive systemic psoriasis therapy or phototherapy. During the first 12 weeks of the study, patients were randomly assigned to receive by subcutaneous injection etanercept twice weekly (BIW) at a dose of 50 mg or 25 mg, or placebo BIW in a double-blind fashion. During the second 12 weeks, all patients received etanercept 25 mg BIW. The primary endpoint was a 75% or greater improvement from baseline in PASI (PASI 75) at 12 weeks. RESULTS: Five hundred and eighty-three subjects were randomized and received at least one dose of study drug. At week 12, a PASI 75 was achieved by 49% of patients in the etanercept 50 mg BIW group, 34% in the 25 mg BIW group, and 3% in the placebo group (P < 0.0001 for each etanercept group compared with placebo). At week 24 (after 12 weeks of open-label 25 mg etanercept BIW), a PASI 75 was achieved by 54% of patients whose dose was reduced from 50 mg BIW to 25 mg BIW, by 45% of patients in the continuous 25 mg BIW group, and by 28% in the group that received placebo followed by etanercept 25 mg BIW. Etanercept was well tolerated throughout the study. CONCLUSIONS: Etanercept provided clinically meaningful benefit to patients with chronic plaque psoriasis, with no apparent decrease in efficacy after dose reduction.     

A randomized trial of etanercept as monotherapy for psoriasis

OBJECTIVE: To determine safety and efficacy of monotherapy with etanercept. DESIGN: Randomized, double-blind, placebo-controlled, multicenter study. SETTING: Outpatient, ambulatory; private practice and university dermatology research centers. PATIENTS: Patients aged at least 18 years, with plaque psoriasis involving 10% or more of body surface area; 148 were screened and 112 were randomly assigned to treatment groups and received study drug. INTERVENTIONS: Patients received placebo or etanercept, 25 mg, subcutaneously twice a week for 24 weeks. Other psoriasis therapies were limited during the study. MAIN OUTCOME MEASURES: Safety measurements included tracking of adverse events and laboratory values. Efficacy was evaluated using the Psoriasis Area and Severity Index (PASI); the primary end point was a 75% improvement in PASI. Other efficacy measurements included patient and physician global assessments and quality-of-life measures. RESULTS: After 12 weeks of treatment, 17 (30%) of the 57 etanercept-treated patients and 1 (2%) of the 55 placebo-treated patients had achieved PASI 75%, and after 24 weeks, 32 (56%) of etanercept-treated patients and 3 (5%) of placebo-treated patients had reached this level (P<.001 for both time points). By 24 weeks, psoriasis was clear or minimal by physician's global assessment in more than 50% of patients who received etanercept. Treatment failure (PASI response <50) occurred in 23% of patients at week 24. All other measures confirmed the efficacy of etanercept. Adverse events were similar among etanercept and placebo groups. CONCLUSION: Etanercept monotherapy provided significant benefit to patients with psoriasis and had a favorable safety profile.     

Two years of experience with etanercept in recalcitrant psoriasis

BACKGROUND: The safety and efficacy of etanercept have been demonstrated in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Placebo-controlled trials have indicated the efficacy of etanercept in moderate to severe psoriasis. OBJECTIVES: To observe the efficacy and safety profile of etanercept in patients with severe psoriasis resistant to other systemic agents over a 2-year period. METHODS: In this retrospective study, 49 patients were treated with etanercept between March 2004 and March 2006. All patients were screened for tuberculosis with tuberculin test and a chest X-ray. Thirty-nine patients started on etanercept 25 mg twice weekly (BIW) and 10 started at 50 mg BIW when judged to be clinically indicated. In 19 of those on 25 mg BIW, the dose was increased to 50 mg BIW because of poor response and psoriasis flaring. Response to treatment was assessed by Psoriasis Area and Severity Index (PASI) and static Physician Global Assessment (PGA). Patients were reviewed at 8-week intervals, when clinical response and adverse effects were noted. RESULTS: Forty-four patients (90%) had chronic plaque psoriasis, two (4%) were suberythrodermic, one (2%) had palmoplantar pustular psoriasis and two (4%) had acrodermatitis continua of Hallopeau. At least 75% reduction in PASI was achieved in 47% of patients at week 24 and 66% at week 48. At week 24, 44% had a PGA score of excellent, and at week 48, 58% scored excellent. In 12 who cleared, etanercept was stopped. Ten of these relapsed and etanercept was recommenced, while two remained in remission (mean 12.5 weeks). One patient developed extrapulmonary tuberculosis. CONCLUSIONS: Etanercept was effective in severe psoriasis recalcitrant to other systemic medication. The drug was well tolerated. Development of tuberculosis in one patient underlines the need for rigorous tuberculosis screening.     

Combining etanercept and acitretin in the therapy of chronic plaque psoriasis: a 24-week, randomized, controlled, investigator-blinded pilot trial

Background Combination treatments may increase efficacy while reducing dosages and side‐effects of individual agents. No randomized controlled trials have been published combining biologics with conventional agents for psoriasis. Objectives To investigate the efficacy and safety of the association of acitretin and etanercept in the treatment of moderate to severe chronic plaque psoriasis. Methods A 24‐week, randomized, controlled, investigator‐blinded pilot trial was conducted. Sixty adult patients with moderate to severe chronic plaque psoriasis were randomized into three groups to receive etanercept 25 mg twice weekly subcutaneously, oral acitretin 0·4 mg kg^?1 daily or etanercept 25 mg once weekly plus acitretin 0·4 mg kg^?1 daily. The primary end point was a 75% or greater improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI 75) at week 24. Results At week 24, PASI 75 response was achieved by 10 of 22 patients in the etanercept group (45%), six of 20 in the acitretin group (30%) and eight of 18 (44%) in the group treated with etanercept plus acitretin (P = 0·001 for both etanercept groups compared with acitretin alone). A 50% or greater improvement from baseline in PASI was achieved by 15 of 22 (68%), 10 of 20 (50%) and 12 of 18 (67%) patients, respectively (P = 0·001). The safety profiles of the three groups were similar. Conclusions A combined therapeutic regimen with etanercept 25 mg once weekly and acitretin 0·4 mg kg^?1 daily is as effective as etanercept 25 mg twice weekly, and more effective than acitretin alone. Although larger studies are needed to confirm these results, the etanercept/acitretin association could offer several advantages in the therapy of moderate to severe chronic plaque psoriasis.     

A randomized, ‘head‐to‐head’ pilot study comparing the effects of etanercept monotherapy vs. etanercept and narrowband ultraviolet B (NB‐UVB) phototherapy in obese psoriasis patients

Background Etanercept is a tumour necrosis factor‐alpha antagonist used for the treatment of moderate‐to‐severe psoriasis. Current opinion suggests that etanercept may have reduced efficacy in obese patients. Narrowband ultraviolet B (NB‐UVB) phototherapy is unaffected by body weight and the addition of NB‐UVB to etanercept therapy may supplement the efficacy of etanercept in these patients. Objective To evaluate the efficacy and safety of NB‐UVB phototherapy when administered in conjunction with 50 mg of etanercept once weekly in the treatment of obese patients with moderate‐to‐severe plaque psoriasis. Methods Thirty psoriasis patients with a body mass index (BMI) greater than 30 were enrolled into this randomized, ‘head‐to‐head’ comparison study. All subjects received 50 mg of etanercept twice weekly for 12 weeks and then randomized to receive either etanercept monotherapy or combination etanercept and NB‐UVB three times weekly for an additional 12 weeks. Treatment response was evaluated using Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician’s Global Assessment (PGA) scores. Results Twenty‐five subjects completed the study. At 12 weeks, 48% of all patients achieved PASI 75. By Week 24, 62.5% of all patients achieved PASI 75. Patients in the etanercept monotherapy and combination etanercept and NB‐UVB phototherapy arms had similar rates of achieving PASI 75 (46.7% vs. 53.3% of each group, respectively). Conclusion Combination etanercept and NB‐UVB has similar efficacy to etanercept monotherapy in obese patients. This result indicates that even in the setting of obesity, the majority of patients respond well to etanercept, with or without NB‐UVB.     

Prevalence of Antigliadin Antibodies in Patients with Psoriasis is Not Elevated Compared with Controls

Background: Antigliadin antibodies (AGAs) are markers of celiac sprue but may have autoimmune implications in the absence of gastrointestinal disease. There is anecdotal evidence to suggest that gluten sensitivity may play a role in psoriasis, and patients with psoriasis in Europe have been reported to improve on a gluten-free diet. Objective: To assess whether patients with psoriasis in the US have an increased prevalence of elevated AGAs. Method: A US sample of patients with psoriasis (n = 100), patients with psoriasis and psoriatic arthritis (n = 100), and age-matched control individuals without any personal or family history of autoimmune disorders (n = 100) were tested for IgG and IgA AGAs. Results: No difference in the prevalence of abnormal AGAs among patients with psoriasis (14%), combined psoriasis and psoriatic arthritis (18%), and control individuals (19%) was observed. No significant correlations between AGA positivity and psoriasis severity, joint involvement, or age of onset of psoriasis or arthritis were observed. Conclusion: We found no support for the results of prior studies showing that elevated AGAs occur with increased frequency in patients with psoriasis. Furthermore, the relatively high prevalence of abnormal AGAs in our control population suggests these antibodies may not be associated with autoimmune disease.     

Efficacy and Safety of Adalimumab among Patients with Moderate to Severe Psoriasis with Co-Morbidities

Background: Psoriasis is associated with a variety of major physical and mental co-morbidities. Objective: To assess the incremental burden of co-morbidities on patient-reported outcomes and evaluate the efficacy and safety of adalimumab in psoriasis patients with co-morbidities. Study Design: Data were obtained from the initial 16-week, double-blind treatment period of REVEAL (Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis triAL), a randomized, multicenter, phase III clinical trial. Intervention: Patients with moderate to severe psoriasis were randomized in a 2 : 1 ratio to receive adalimumab 80 mg (two 40 mg injections administered subcutaneously) at baseline followed by one 40 mg injection every other week from week 1 to week 15 or placebo. Main Outcome Measures: Clinical severity (Psoriasis Area and Severity Index [PASI]) and patient-reported outcomes (Dermatology Life Quality Index [DLQI], Short Form 36 [SF-36] health survey, Work Productivity and Activity Impairment [WPAI] questionnaire) were assessed during the trial. The effect of selected co-morbidities (i.e. hypertension, psoriatic arthritis, hyperlipidemia, obesity, depression, other forms of arthritis, diabetes mellitus, and other cardiovascular diseases) on patient-reported outcomes was evaluated using multivariate analysis of covariance models. Subgroup analyses were performed by co-morbidity type to statistically compare the clinical efficacy, patient-reported outcome benefits, and safety of adalimumab with placebo in the presence of these conditions. Results: Study co-morbidities were each independently associated with significantly greater impairment on at least one general patient-reported outcome measured at baseline (all p < 0.05), with the exception of hyperlipidemia. During the 16-week study, adalimumab patients demonstrated significantly greater PASI 75 response rates (defined as a reduction of at least 75% in PASI scores from baseline) compared with placebo patients for all co-morbidity subgroups. Adalimumab provided consistent improvements in DLQI, SF-36 Physical Component Summary and Mental Component Summary scores, and WPAI total scores from baseline to week 16 within co-morbidity subgroups. Rates of serious adverse events (AEs), serious infectious AEs, and AEs leading to discontinuation were comparable between adalimumab and placebo for patients with co-morbidities. Conclusions: Co-morbidities were associated with additionally impaired health-related quality of life and work productivity in patients with psoriasis. Adalimumab significantly improved efficacy and patient-reported outcomes and was well tolerated in patients with co-morbidities.     

Once weekly administration of etanercept 50 mg is efficacious and well tolerated in patients with moderate-to-severe plaque psoriasis: a randomized controlled trial with open-label extension

Background In previous studies, etanercept 25 mg twice weekly (BIW) or 50 mg BIW significantly reduced disease severity in patients with plaque psoriasis and demonstrated a favourable safety profile. Objectives To assess the efficacy and safety of etanercept 50 mg administered once weekly (QW) compared with placebo in patients with moderate‐to‐severe plaque psoriasis over 24 weeks. Methods This study was conducted in two parts: (i) a 12‐week, double‐blind, placebo‐controlled phase, in which patients received etanercept 50 mg QW or placebo QW; and (ii) a 12‐week, open‐label extension phase, in which all patients received etanercept 50 mg QW. Primary endpoint was a 75% or greater improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at week 12. Secondary endpoints included percentage PASI improvement and Physician’s Global Assessment (PGA). Results One hundred and forty‐two patients were analysed in the double‐blind phase; 126 patients entered the open‐label phase. At week 12, significantly more patients receiving etanercept 50 mg QW (37·5%) achieved PASI 75 response than patients receiving placebo (2·2%; P < 0·0001). At week 24, 71·1% in the etanercept–etanercept group and 44·4% in the placebo–etanercept group achieved PASI 75. Mean percentage of PASI improvement from baseline was 55·4% with etanercept vs. 9·4% worsening with placebo at week 12 (P < 0·0001), with 77·4% and 57·7% improvement in the etanercept–etanercept and placebo–etanercept groups at week 24. A PGA score of 0–1 (clear–almost clear) was achieved by 64% and 42% in the etanercept–etanercept and placebo–etanercept groups at week 24, respectively. Etanercept 50 mg QW was well tolerated. No deaths, serious infections, opportunistic infections (including tuberculosis), demyelinating disorders, malignancies or new safety signals were reported. Conclusions Nearly three‐quarters of patients with moderate‐to‐severe psoriasis receiving etanercept 50 mg QW achieved significant improvement in disease severity over 24 weeks. This study also showed a favourable tolerability and safety profile with etanercept 50 mg QW.     

Placebo Response in Two Long-Term Randomized Psoriasis Studies that were Negative for Rosiglitazone

Background:Previous research has suggested that the thiazolidinedione rosiglitazone may possess antipsoriatic activity. Objective:To compare the efficacy and safety of rosiglitazone with that of placebo in the treatment of chronic plaque psoriasis. Methods:Two large-scale, randomized, double-blind, multicenter studies (study A, n = 1563; study B, n = 1032) were conducted over 52 weeks (plus optional 44 weeks safety extension) in an outpatient setting. The subjects (aged 18–75 years) had moderate-to-severe chronic plaque psoriasis affecting ≥10% body surface area (BSA) with plaques of any elevation above normal-appearing skin (or ≥6% BSA involvement with marked elevation) and had not used phototherapy during the previous month or thiazolidinediones within the previous 3 months. Rosiglitazone was administered as 2, 4, or 8mg tablets once daily. The main outcome measure was the proportion of subjects achieving ≥75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at week 26. both studies for subjects receiving placebo, the PASI 75 was 9% (48/506) and the PASI 50 (proportion of subjects who achieved at least 50% improvement from baseline) was 27% (135/506). In addition, few subjects withdrew from placebo or rosiglitazone treatment because of ‘lack of efficacy’ and the majority persisted in the year-long study. Conclusion: While these large-scale, robust studies demonstrated that rosiglitazone is not active in psoriasis, they also showed that for a large proportion of subjects receiving placebo, the expectation of a successful treatment, the favorable adverse effect profile of the drug, and the supportive environment of a clinical study conferred beneficial effects. These results may have implications for the design of future placebo-controlled studies in patients with psoriasis.     

Combination of skin,joint and quality of life outcomes with etanercept in psoriasis and psoriatic arthritis in the PRESTA trial

Background Psoriasis and psoriatic arthritis (PsA) affect skin, and/or joints and quality of life (QoL). Objective To better assess the success in multiple attributes in subjects with both active psoriasis and PsA, the objective was to quantify the proportion of those who achieved substantial improvement in a composite measure of skin symptoms, joint manifestations, and QoL, on one of two treatment regimens. Methods Subjects (n = 752) with psoriasis and PsA (mean age: 46.5 years, 62.9% male) received etanercept (ETN) 50 mg twice weekly (BIW; n = 379) or 50 mg weekly (QW; n = 373) for 12 weeks, followed by open‐label ETN 50 mg QW for 12 weeks. Skin and joint symptoms and QoL were assessed using psoriasis area and severity index (PASI), American College of Rheumatology criteria (ACR) and Euro‐QoL (EQ‐5D), respectively. Results By week 24, 30.6% and 25.8% of subjects receiving ETN 50 mg BIW/QW and ETN 50 mg QW/QW, respectively (P = 0.198) achieved the composite measure of efficacy for skin plus joints plus QoL (PASI 75 + ACR 50 + EQ‐5D VAS >82). Conclusion At 24 weeks, 25.8–30.6% met the triad of rigorous efficacy outcomes. Evaluation of treatment efficacy should address the multiple components of this disease complex; therefore it may be important to consider this composite measure in future trials.     

Etanercept use for psoriasis in Taiwan: a case series study

Background The reported efficacy and safety of some biologic agents for psoriasis vary between Caucasians and Asians. Few reports of etanercept exist in psoriasis patients within the Asia‐Pacific region. Objectives The study aims to report our clinical experience of etanercept in the treatment of patients with moderate‐to‐severe psoriasis in Taiwan. Methods A retrospective analysis of 59 patients with moderate‐to‐severe psoriasis who received etanercept was conducted in a tertiary referral center. Results Etanercept therapy resulted in a reduction of mean Psoriasis Area and Severity Index (PASI) of 47% at week 12 and 61% at week 24. After 12 weeks of treatment, 48%, 26%, and 3.4% of the patients achieved at least PASI50, 75 and 90 response, respectively. At week 24, the proportion of patients achieving at least PASI50, 75 and 90 response was 59%, 37%, and 14%, respectively. Etanercept efficacy in achieving PASI75 improvement was, however, lower than that reported in previous pivotal placebo‐controlled trials. No cases of active tuberculosis, viral hepatitis or malignancies were observed during the observation period. Conclusion Our case series demonstrated the efficacy and safety of etanercept for the management of moderate‐to‐severe psoriasis in Taiwan.     

Quality of Life and Treatment Satisfaction among Patients with Psoriasis and Psoriatic Arthritis and Patients with Psoriasis Only

Introduction: Five to forty percent of patients with cutaneous psoriasis develop an inflammatory, oligoarticular spondyloarthropathy known as psoriatic arthritis. Objective: To compare health-related quality of life (QOL) between cutaneous psoriatic patients with and without psoriatic arthritis. Method: Secondary cross-sectional analysis of data obtained from the 2005 Spring US National Psoriasis Foundation Quality of Life Telephone/Internet Survey. 426 patients with psoriasis and/or psoriatic arthritis were included in the 2005 survey. Among these respondents, the self-reported disease histories of 140 patients with cutaneous psoriasis and psoriatic arthritis were compared with those of 278 patients with cutaneous psoriasis only. Both groups were compared with respect to demographics, skin disease severity, treatment history and satisfaction, and QOL using previously validated assessment scales. Results: Compared with those with skin psoriasis only, respondents with cutaneous psoriasis and psoriatic arthritis were slightly older, more likely to be female and members of the National Psoriasis Foundation, and more likely to report a younger age of disease onset. They were also more likely to be unemployed, to report their job was affected by their condition, and to report a higher mean estimate of lost annual wages. On both univariate and multivariate analysis, however, no significant differences between groups were detected in skin disease severity, overall QOL, and satisfaction with current treatment options. At the same time, individuals with skin psoriasis and psoriatic arthritis were more likely to be taking systemic agents. They also reported higher mean scores for pain, while those with cutaneous psoriasis reported higher mean scores for self-consciousness only. Conclusion: In contrast to previous reports that did not control for skin disease severity, this study demonstrates that patients with cutaneous psoriasis and psoriatic arthritis do not report significantly worse health-related QOL compared with patients with cutaneous psoriasis only. Nor do they report significantly greater dissatisfaction with current treatment options. These findings may reflect the intrinsic inadequacy of the QOL instruments used in this study for capturing the additional burden of joint disease. Alternatively, these findings may reflect the existence of a threshold of joint disease in patients with skin psoriasis and psoriatic arthritis below which joint symptoms are perceived as negligible relative to cutaneous disease.